{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T02:14:11Z","timestamp":1787019251011,"version":"build-2736575974"},"reference-count":35,"publisher":"SAGE Publications","issue":"2","license":[{"start":{"date-parts":[[2022,5,29]],"date-time":"2022-05-29T00:00:00Z","timestamp":1653782400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"funder":[{"name":"Praxis Pharmaceutical S.A"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["The International Journal of Lower Extremity Wounds"],"published-print":{"date-parts":[[2025,6]]},"abstract":"<jats:p>Negatively charged polystyrene microspheres (NCMs) have been demonstrated as a novel and effective therapy for managing hard-to-heal diabetic foot ulcers (DFUs). However, one limitation of this therapy is that the protocol is based on daily application, which sometimes does not fit local protocols of wound care. Thus, we aimed to analyze the safety and efficacy of a new dose regimen. We conducted a randomized blinded controlled trial in a specialized diabetic foot unit between May 2019 and February 2021 with a total of 30 patients who had neuropathic or neuroischemic DFUs that had not responded after four weeks of standard treatment. Patients were randomized consecutively into a group that received daily application (control) or one that received applications three times per week (experimental). The clinical outcomes were evaluated using the Wollina score and wound-area reduction (WAR) weekly during a treatment period of 28 days. The histological outcomes were assessed using a soft-tissue punch biopsy (3\u2005mm) at 0, 14, and 28 days to evaluate cellular proliferation. The Wollina scores were higher at the end of treatment by week 4 in both groups, but the differences were not significant between groups. The averages were 6 (5, 7) points in Experimental group (EG) and 6 (6,7) points in Control group (CG) (p\u2009=\u20090.848). Wound area reduction at day 28 was 53.57 [37.43, 79.16] % in the CG and 79.37 [42.74, 93.57] % in the EG, without differences among groups (p\u2009=\u20090.305). Cellular proliferation was similar in both groups at day 28. Application three times per week showed similar clinical and histological outcomes to those of daily application, both dose regimens demonstrated significant improvement of granulation tissue formation and WAR during the treatment.<\/jats:p>","DOI":"10.1177\/15347346221104946","type":"journal-article","created":{"date-parts":[[2022,5,30]],"date-time":"2022-05-30T02:24:07Z","timestamp":1653877447000},"page":"488-496","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":2,"title":["Clinical and Histological Outcomes of Negatively Charged Polystyrene Microspheres Applied Daily Versus Three Times per Week in Hard-to-Heal Diabetic Foot Ulcers: A Randomized Blinded Controlled Trial"],"prefix":"10.1177","volume":"24","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6110-0265","authenticated-orcid":false,"given":"Jos\u00e9 Luis","family":"L\u00e1zaro-Mart\u00ednez","sequence":"first","affiliation":[{"name":"Diabetic Foot Unit, Cl\u00ednica Universitaria de Podolog\u00eda, Facultad de Enfermer\u00eda, Fisioterapia y Podolog\u00eda, Universidad Complutense, Instituto de Investigaci\u00f3n Sanitaria del Hospital Cl\u00ednico San Carlos (IdISSC), Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7349-7378","authenticated-orcid":false,"given":"Marta","family":"Garc\u00eda-Madrid","sequence":"additional","affiliation":[{"name":"Diabetic Foot Unit, Cl\u00ednica Universitaria de Podolog\u00eda, Facultad de Enfermer\u00eda, Fisioterapia y Podolog\u00eda, Universidad Complutense, Instituto de Investigaci\u00f3n Sanitaria del Hospital Cl\u00ednico San Carlos (IdISSC), Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7342-059X","authenticated-orcid":false,"given":"Mateo","family":"L\u00f3pez-Moral","sequence":"additional","affiliation":[{"name":"Diabetic Foot Unit, Cl\u00ednica Universitaria de Podolog\u00eda, Facultad de Enfermer\u00eda, Fisioterapia y Podolog\u00eda, Universidad Complutense, Instituto de Investigaci\u00f3n Sanitaria del Hospital Cl\u00ednico San Carlos (IdISSC), Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5650-7351","authenticated-orcid":false,"given":"Aroa","family":"Tard\u00e1guila-Garc\u00eda","sequence":"additional","affiliation":[{"name":"Diabetic Foot Unit, Cl\u00ednica Universitaria de Podolog\u00eda, Facultad de Enfermer\u00eda, Fisioterapia y Podolog\u00eda, Universidad Complutense, Instituto de Investigaci\u00f3n Sanitaria del Hospital Cl\u00ednico San Carlos (IdISSC), Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4674-3822","authenticated-orcid":false,"given":"Francisco Javier","family":"\u00c1lvaro-Afonso","sequence":"additional","affiliation":[{"name":"Diabetic Foot Unit, Cl\u00ednica Universitaria de Podolog\u00eda, Facultad de Enfermer\u00eda, Fisioterapia y Podolog\u00eda, Universidad Complutense, Instituto de Investigaci\u00f3n Sanitaria del Hospital Cl\u00ednico San Carlos (IdISSC), Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1424-5087","authenticated-orcid":false,"given":"Yolanda","family":"Garc\u00eda-\u00c1lvarez","sequence":"additional","affiliation":[{"name":"Diabetic Foot Unit, Cl\u00ednica Universitaria de Podolog\u00eda, Facultad de Enfermer\u00eda, Fisioterapia y Podolog\u00eda, Universidad Complutense, Instituto de Investigaci\u00f3n Sanitaria del Hospital Cl\u00ednico San Carlos (IdISSC), Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2022,5,29]]},"reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMra1615439"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1002\/dmrr.2319"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1177\/1534734610380029"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1007\/s40257-019-00495-x"},{"issue":"1","key":"e_1_3_3_6_2","article-title":"Practical guidelines on the prevention and management of diabetic foot disease (IWGDF 2019 update)","volume":"36","author":"Schaper NC","year":"2020","unstructured":"Schaper NC, van Netten JJ, Apelqvist J, Bus SA, Hinchliffe RJ, Lipsky BA. 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